Hepatic uptake and excretion of [ 14C]sodium taurocholate by the isolated perfused fetal sheep liver

We have developed an in situ isolated perfused fetal sheep liver preparation to study fetal hepatic function free from the confounding influences of the mother and other fetal organs, and we have used the preparation to study the fetal hepatic clearance and biliary excretion of sodium taurocholate (TC). The viability and stability of this model were established by monitoring perfusion pressure, oxygen consumption, perfusate enzymes and electrolytes, the perfusate concentration ratio of lactate to pyruvate, bile flow, and liver histology. Perfusate delivery was 300mL/min with a mean value of 3.94 mL/min/g liver (range: 2.46–6.72 mL/min/g liver). Gadolinium radiolabeled 15μm microspheres were used to quantify the ductus venosus shunt through the liver and to determine relative flow rates between right and left hepatic lobes. TC was added to the reservoir either as a [ 14C]TC tracer bolus dose (2 μCi, N = 5) followed by a constant infusion of unlabeled TC, or as an initial bolus of [ 14C]TC (54μmol) followed by a [ 14C]TC constant infusion (30 μmol/hr, specific activity 30 μCi/mmol; ( N = 3). Perfusate samples were taken from the reservoir every 15 min and bile was collected in 30 min aliquots. Perfusion pressure (7.9 ± 0.30 mmHg), perfusate potassium and oxygen consumption (0.9 ± 0.07 μmol/min/g liver) were constant throughout, and the perfusate lactate/pyruvate concentration ratio was low (